Three related problems will be studied: (1) Neutralization of viruses by antibody: A hypothesis has been proposed to explain the mechanism of neutralization of poliovirus. Other viruses will be studied to test the generality of the hypothesis which, in essence, states that one molecule of antibody per virion is sufficient to induce a conformational rearrangement of the capsid which renders it resistant to uncoating. These studies will entail infectivity and electrophoretic analyses of native and neutralized virus. (2) Uncoating: Release of viral genome is an early stage in replication. The responsible cellular components and the mechanism of this reaction will be studied. An in vitro system has been developed capable of modifying the viral capsid which is the first stage of the uncoating process. The active component is a membrane-rich extract of HeLa cells. The in vitro system will be studied, (a) to identify the active component of the extract, (b) to characterize the modification in the capsid, (c) to characterize the reaction mechanism. Studies will be undertaken to obtain from HeLa cells a component capable of acting on the modified virion and completing the uncoating process. (3) Characteristics of the viral capsid: The capsid protein will be studied specifically in respect to its bearing on the above problems. Principally the studies will concern conditions that are conducive to the dissociation of the capsid without detriment to the genome.